216880-29-4Relevant academic research and scientific papers
Enzyme-controlled molecular recognition: Selective targeting of trypsin with a substrate-inhibitor supramolecular complex
Rudra, Sonali,Eliseev, Alexey V.
, p. 11543 - 11547 (1998)
We have synthesized and studied the host compound (1) that forms a noncovalent complex (K = 480 ± 30 M-1) with 1,4-diamidinobenzene (2) at pD 8.0 in D2O. Guest 2 has been shown to inhibit the proteases specific for cationic side chains (K(i) values for thrombin, plasmin, and trypsin being 1.0 ± 0.4, 0.6 ±0.1, and 0.88 ± 0.07 mM, respectively). Host 1 and the 1- 2 complex are shown to undergo the trypsin-catalyzed cleavage that results in the increased concentration of the free form of 2 and, therefore, induces the enzyme inhibition. Plasmin and thrombin are shown to cleave 1 at a significantly lower rate than trypsin. Thus, the complex of 1 with 2 represents the first example of a selective enzyme-sensitive supramolecular system capable of enzyme targeting through a 'trojan horse'-type mechanism in which a bioactive compound acts on the same molecule that provides its release from a delivery system.
